1. Field of the Invention
The invention relates to the field of magnetic resonance imaging for obtaining a graphic representation of biological samples and other materials, such as polymers, etc. (hereinafter, the "sample" or the "specimen"). In connection with graphic representation of tissue and the like, the invention provides a diagnostic tool for visualizing ischemia, infarction and other irregularities in cerebral and noncerebral tissues. However, the invention is useful for visualizing the microstructure of materials generally. More particularly, the invention employs phase angle reconstruction imaging techniques using paramagnetic contrast agents for improving the accuracy of the image data collected for each volume element in an image slice.
2. Prior Art
Magnetic resonance imaging is a non-invasive and non-destructive testing procedure whereby local variations in the electromagnetic properties of a specimen can be detected and displayed, for example, as variations in the luminance or color of pixels in an image. In general, magnetic resonance imaging involves applying bursts of radio frequency energy to a specimen positioned in a main magnetic field in order to produce responsive emission of electromagnetic radiation from hydrogen nuclei or other nuclei. The emitted signal is sampled over time after a predetermined time delay following an illuminating pulse, the time delay being chosen to highlight magnetically responsive atoms. The collected signal is digitized, producing a time domain representation of the specimen, typically through a plane or slice of predetermined thickness. By Fourier transform analysis the time domain representation is converted into a spatial representation of the slice, which is then displayed as an X-Y array of pixels. Whereas certain atoms contained in tissues are magnetically responsive at particular echo times and others are not, the resulting data can be used to distinguish between types of tissue, using the electromagnetic response of the tissue as the distinguishing parameter.
A plurality of slices can be recorded in this manner, for obtaining a three dimensional representation of the internal character of the specimen. The distinct magnetic properties of the tissues are mapped to identify variations in anatomical structures. For example, the iron content in blood renders the blood more susceptible to magnetization than surrounding tissues, providing a means by which vascular structures can be distinguished. There are many particular methods by which data collected in this manner can be analyzed to produce useful information, with better detail than can be obtained from ultrasound imaging, without subjecting the specimen to ionizing radiation, and without undertaking surgery.
The Fourier transform involves converting the in-phase and out-of-phase signal amplitudes as a function of time to complex signal intensity as a function of frequency, from which the magnitude of the complex signal is derived. The magnitude data may be displayed without enhancement, but enhancement is valuable for presenting the information in variations of luminance, saturation and/or hue corresponding to structural variations thereby detected in heterogeneous tissue or the like. A specific technique for spin echo magnetic resonance imaging is disclosed, for example, in U.S. Pat. No. 4,766,381--Conturo et al. Once the raw data is available in the form of amplitude samples, various techniques can be employed for extracting useful data. However, there are certain limitations in the data due to the interaction of fields produced in neighboring tissues, motion in the blood vessels, etc.
In connection with certain conditions, a magnetic resonance image can be analyzed by skilled persons to visualize the location, size and character of tumors, hematomas, infarctions and the like, due to the spatially discontinuous response of such structures and/or the blood flow in the region to a pulsed radio frequency signal. For example, a localized area of anemic tissue may occur in connection with an infarction, and be identifiable as distinct from healthy surrounding tissue. The localized area or the perimeter of the area is characterized by a different magnetic susceptibility as a result of accumulation or scarcity of paramagnetic elements as compared to the healthy tissue. In the area of an injury, breakdown products of blood may accumulate, including deoxyhemoglobin, methemoglobin, free ferric iron, hemosiderin and the like.
Magnetic susceptibility data for imaging tissues including paramagnetic elements can be obtained by measuring the amplitude of transverse magnetization that remains after a change is induced by an incident radio frequency field. The net transverse decay rate differs for different areas of heterogeneous tissue, as a function of the local concentration and distribution of paramagnetic material.
It is possible to increase the contrast of a magnetic resonance image by infusing a paramagnetic material which has a different distribution in the structure of interest than the distribution in adjacent structures. Use of an exogenous agent to improve amplitude contrast is disclosed, for example, in "Perfusion Imaging with NMR Contrast Agents," Rosen et al, 14 Magnetic Resonance in Medicine 249-265 (1990).
Paramagnetic infusion can be effected by slow intravenous injection of an accumulating paramagnetic material, or by faster injection of a quantity of the paramagnetic material (i.e., a bolus), which travels through the blood stream. By recording a plurality of magnetic resonance images both before and during the perfusion of the tissues with blood carrying the paramagnetic contrast agent, it is possible to obtain a baseline image which can be subtracted from or divided into the signal magnitude data representing an image recorded during perfusion, thereby substantially enhancing the contrast and the detail of the particular structure of interest.
Subtraction of a baseline image from an image recorded during perfusion with an x-ray absorptive agent is known in connection with angiography. See, e.g., the references mentioned in "Projectire Imaging of Pulsatile Flow with Magnetic Resonance," Wedeen et al, 230 Science 946-948 (1985). This article also discusses subtracting a baseline magnetic resonance complex image from a second image, the magnitude difference of which highlights moving elements (i.e., blood flow). The motion of the blood is detectable as magnitude signal changes which result from phase variation caused by the motion, producing a high contrast image of vascular structures. However, the article does not discuss the possibility of relating contrast agents to magnetic resonance phase mapping, particularly in connection with phase angle reconstruction and baseline phase angle subtraction.
Magnetic susceptibility-weighted magnitude magnetic resonance images can be used in conjunction with bolus injection of paramagnetic contrast agents to assess the effects of cerebral perfusion. By rapidly acquiring such images (including at the time of passage of the bolus), functional aspects of cerebral blood flow can be identified. With a bolus injection, the paramagnetic agent is confined to the vascular space during passage through the brain, and later becomes diffused through the tissues in the remainder of the body.
Within the blood vessel, a bulk magnetic field shift is produced due to the paramagnetic susceptibility of the contrast agent. Field gradients occur around concentrations of the agent, e.g., around blood vessels. In a particular volume element (or "voxel") of brain parenchyma from which an image pixel is derived, there are complex field inhomogeneities that are not all due to corresponding inhomogeneities in the tissue structure or to inhomogeneities in the externally applied static field. The variations in field gradients produce signal dephasing that degrades the magnitude reconstructed signal of a magnetic resonance image. The signal loss depends on the statistical distribution of fields within the voxel (e.g., Gaussian vs. Lorentsian), and thus depends on factors such as the size, density and heterogeneity of capillaries as well as temporal concentration changes, multiexponential T.sub.2 decay, diffusion and other factors.
The present invention is directed to phase reconstruction of an image rather than magnitude (amplitude) reconstruction, and thus relies on the variation in electromagnetic phase response of different tissues. Bulk magnetic susceptibility variations from tissue to tissue and variations due to hyperfine electron-nuclear coupling are enhanced by introduction of a paramagnetic contrast agent. The contrast agent causes resonance frequency shifts and field-frequency offsets which are detected as phase shifts using a phase angle reconstruction of the sampled data, preferably with subtraction of baseline data collected either before introduction of the contrast agent or after the contrast agent has diffused to the point that local inhomogeneities have dissipated.
The net phase is relatively insensitive to the intra-voxel field distribution, provided that the field distribution has a symmetric (e.g., statistical) profile, and thus can improve over results obtained in magnitude reconstruction, where many confounding factors contribute to signal dephasing. Paramagnetic-induced heterogeneities can be expected to induce different responses as to magnitude and phase, but the insensitivity of phase to at least some of these variations is such that phase reconstruction is believed to have better accuracy than magnitude reconstruction. Moreover, the phase images are better in a diagnostic setting, for example because the unaffected grey matter appears to have a more uniform brightness.
There are a limited number of examples where phase angle data has been collected for reconstruction of images representing variations in magnetic susceptibility. Such phase data has been used to image susceptibility variations which are endogenous to the brain, whereas the present invention provides a method by which phase angle reconstruction can be applied to exogenous paramagnetic enhancement, with favorable results as explained more fully hereinafter.